It is estimated that in 2013 over 75,000 Americans will be diagnosed with melanoma and almost 10,000 will die of advanced metastatic disease. Recent research has revealed a variety of molecular subtypes of melanoma that may respond differently to targeted therapeutic agents, such as vemurafenib for BRAF mutant tumors. Unfortunately, virtually all of these patients relapse quickly due to the emergence of resistance. Existing clinical assays provide insight into possible therapies for some patients, but most patients with metastatic melanoma do not ultimately benefit from personalized therapy, particularly in the setting of relapsed disease. Functional assays using live tumor cells have demonstrated the potential to provide better information on targeted therapy selection than traditional methods. This project will develop PathMAP, a functional companion diagnostic test to predict optimal therapy for melanoma patients. Its objectives include the refinement of the biomarker assay and ex vivo test protocols developed in Phase I using murine tumorgrafts of primary human tumors followed by PathMAP test validation in human clinical samples.